Ryanodine receptor clusters and heart disease

Structural and functional characterisation of ryanodine receptor clusters in rabbit ventricular myocytes after pathological hypertrophic remodelling

The release of calcium inside heart muscle cells is important for a normal heart beat, and abnormal calcium release can lead to heart rhythm disturbances (arrhythmias). In this Intermediate Basic Science Fellowship, Dr Neil MacQuaide from the University of Glasgow, will investigate how a protein that controls calcium release, called the ryanodine receptor, is altered in heart disease, predisposing to arrhythmias. The ryanodine receptor regulates the release of calcium from a large internal store in the cell. Recently developed microscope techniques allowing scientists to visualise single proteins in cells have shown that ryanodine receptors cluster together forming functional units in the cell. This clustering is thought to be important for the calcium release process. Dr MacQuaide will investigate how the form and function of ryanodine receptor clusters change in heart disease. He will use special fluorescence microscopy techniques and measurements of the fluxes of calcium inside a cell to study these receptors. He will find out how the ryanodine receptor clusters change in response to drugs used against abnormal heart rhythms and he will exploit sophisticated computer modelling approaches to help with these analyses. This detailed study of ryanodine protein clusters will inform future diagnosis and treatment of heart disease.